Serum potassium and adverse outcomes across the range of kidney function: a CKD Prognosis Consortium meta-analysis
European Heart Journal

Abstract
Both hypo- and hyperkalaemia can have immediate deleterious physiological effects, and less is known about long-term risks. The objective was to determine the risks of all-cause mortality, cardiovascular mortality, and end-stage renal disease associated with potassium levels across the range of kidney function and evaluate for consistency across cohorts in a global consortium.
We performed an individual-level data meta-analysis of 27 international cohorts [10 general population, 7 high cardiovascular risk, and 10 chronic kidney disease (CKD)] in the CKD Prognosis Consortium. We used Cox regression followed by random-effects meta-analysis to assess the relationship between baseline potassium and adverse outcomes, adjusted for demographic and clinical characteristics, overall and across strata of estimated glomerular filtration rate (eGFR) and albuminuria. We included 1 217 986 participants followed up for a mean of 6.9 years. The average age was 55 ± 16 years, average eGFR was 83 ± 23 mL/min/1.73 m2, and 17% had moderate- to-severe increased albuminuria levels. The mean baseline potassium was 4.2 ± 0.4 mmol/L. The risk of serum potassium of >5.5 mmol/L was related to lower eGFR and higher albuminuria. The risk relationship between potassium levels and adverse outcomes was U-shaped, with the lowest risk at serum potassium of 4–4.5 mmol/L. Compared with a reference of 4.2 mmol/L, the adjusted hazard ratio for all-cause mortality was 1.22 [95% confidence interval (CI) 1.15–1.29] at 5.5 mmol/L and 1.49 (95% CI 1.26–1.76) at 3.0 mmol/L. Risks were similar by eGFR, albuminuria, renin–angiotensin–aldosterone system inhibitor use, and across cohorts.
Outpatient potassium levels both above and below the normal range are consistently associated with adverse outcomes, with similar risk relationships across eGFR and albuminuria.
Contributors

Csaba P Kovesdy
Author

Kunihiro Matsushita
Author

Yingying Sang
Author

Nigel J Brunskill
Author

Juan J Carrero
Author

Gabriel Chodick
Author

Takeshi Hasegawa
Author

Hiddo L Heerspink
Author

Atsushi Hirayama
Author

Gijs W D Landman
Author

Adeera Levin
Author

Dorothea Nitsch
Author

David C Wheeler
Author

Josef Coresh
Author

Stein I Hallan
Author

Varda Shalev
Author

Morgan E Grams
Author

Brad Astor
Author

Larry Appel
Author

Tom Greene
Author

Teresa Chen
Author

John Chalmers
Author

Mark Woodward
Author

Hisatomi Arima
Author

Vlado Perkovic
Author

Adeera Levin
Author

Ognjenka Djurdjev
Author

Luxia Zhang
Author

Lisheng Liu
Author

Minghui Zhao
Author

Fang Wang
Author

Jinwei Wang
Author

Adeera Levin
Author

Ognjenka Djurdjev
Author

Mila Tang
Author

Hiroyasu Iso
Author

Kazumasa Yamagishi
Author

Mitsumasa Umesawa
Author

Isao Muraki
Author

Masafumi Fukagawa
Author

Shoichi Maruyama
Author

Takayuki Hamano
Author

Takeshi Hasegawa
Author

Naohiko Fujii
Author

David Wheeler
Author

John Emberson
Author

John Townend
Author

Martin Landray
Author

Jamie Green
Author

H Lester Kirchner
Author

Alex R Chang
Author

Massimo Cirillo
Author

Sun Ha Jee
Author

Heejin Kimm
Author

Yejin Mok
Author

Gabriel Chodick
Author

Varda Shalev
Author

Jack F M Wetzels
Author

Peter J Blankestijn
Author

Arjan D van Zuilen
Author

M Bots
Author

Mark Sarnak
Author

Lesley Inker
Author

Dorothea Nitsch
Author

Paul Roderick
Author

Astrid Fletcher
Author

Erwin Bottinger
Author

Girish N Nadkarni
Author

Stephen B Ellis
Author

Rajiv Nadukuru
Author

Yingying Sang
Author

Nigel Brunskill
Author

Rupert Major
Author

David Shepherd
Author

James Medcalf
Author

Ron T Gansevoort
Author

Stephan J L Bakker
Author

Hiddo J Lambers Heerspink
Author

Simerjot K Jassal
Author

Jaclyn Bergstrom
Author

Joachim H Ix
Author

Elizabeth Barrett-Connor
Author

Csaba Kovesdy
Author

Kamyar Kalantar-Zadeh
Author

Hiddo J Lambers Heerspink
Author

Dick de Zeeuw
Author

Barry Brenner
Author

Juan J Carrero
Author

Alessandro Gasparini
Author

Carl-Gustaf Elinder
Author

Peter Barany
Author

Marie Evans
Author

Mårten Segelmark
Author

Maria Stendahl
Author

Staffan Schön
Author

Navdeep Tangri
Author

Maneesh Sud
Author

David Naimark
Author

Chi-Pang Wen
Author

Chwen-Keng Tsao
Author

Min-Kugng Tsai
Author

Chien-Hua Chen
Author

Tsuneo Konta
Author

Atsushi Hirayama
Author

Kazunobu Ichikawa
Author

Henk J G Bilo
Author

Gijs W D Landman
Author

Kornelis J J van Hateren
Author

Nanne Kleefstra
Author

Josef Coresh
Author

Ron T Gansevoort
Author

Morgan E Grams
Author

Stein Hallan
Author

Csaba P Kovesdy
Author

Andrew S Levey
Author

Kunihiro Matsushita
Author

Varda Shalev
Author

Mark Woodward
Author

Shoshana H Ballew
Author

Jingsha Chen
Author

Josef Coresh
Author

Morgan E Grams
Author

Lucia Kwak
Author

Kunihiro Matsushita
Author

Yingying Sang
Author

Mark Woodward
Author
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